Abstract

Ovarian cancer has seen a modest improvement in five-year survival over the past three decades. It is well known that the lack of further success is solely due to the advanced stage at diagnosis for most women with ovarian cancers. To reduce the burden of ovarian cancer, we must decrease the incidence (primary prevention), improve early detection (secondary prevention), or develop more effective treatments for newly diagnosed disease (tertiary prevention). Large scale screening trials using traditional methods of imaging and tumor markers have not led to meaningfully stage migration, reduction in mortality, or widespread clinical adoption. In fact, the FDA recently issued a safety alert about the risks associated with the use of tests being marketed as ovarian cancer screening tests. The FDA was specifically concerned about ovarian cancer screening tests being used in lieu of established risk-reduction approaches.

This presentation will review practical approaches to reducing the burden of ovarian cancer through primary, secondary, and tertiary prevention. Genetic testing of probands for BRCA1 and BRCA2 germline mutations alone and cascade testing of relatives are currently available approaches to reduce the incidence of ovarian cancer by more than 10%. This tactic is consistent with professional guidelines and has the added advantage of identifying therapeutic options for ovarian cancer patients that could contribute to tertiary prevention efforts today and in the future. Lower penetrant genes also have the potential to lead to primary prevention through risk reduction strategies, but further data is required to firmly establish appropriate age-based recommendations. The identification of the distal fallopian tube as a likely site of origin for most ovarian cancers has opened a new domain for ovarian cancer primary prevention. Some governmental organizations suggest population-based bilateral salpingectomy at the time of any pelvic or abdominal surgery for primary prevention of ovarian cancers considering that one-third of US women will have a hysterectomy by age 70. The reasons for success and failure of this approach will be discussed.

The fallopian tube as the site of origin for ovarian cancers has led to new approaches for early detection. The anatomy of the fallopian tube and its proximity to the lower genital tract has led to the development of creative strategies for sampling derivatives of precursor lesions and early invasive disease. Collection of uterine fluid for proteomic analyses and DNA sequencing holds promise for enrichment of cancer-specific biomolecules. Cervical pap smears and the collection of vaginal secretions offer a less invasive approach to early detection through similar theoretical avenues. Through the study of long-term survivors of advanced stage high-grade serous ovarian cancer, we have learned that primary surgical cytoreduction reduces the risk of cancer recurrence and serves as a useful approach to tertiary prevention.